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Poster Full Abstracts - Cell Death
Poster board number is above title. The first author is the presenter
217
314B
The Role of JNK in Cell Competition.
John F Fullard, Wei Li, Nicholas E Baker. Department of Genetics, Albert Einstein College of Medicine, Bronx,
NY.
JNK signalling has been implicated in cell death in cell competition. We describe the non-autonomous requirement for JNK signalling, not in the M/+ cells
that die, but in the nearby wild type cells that kill them. Draper and Shark, components of the ced-1,6,7 pathway in Drosophila, activate the JNK pathway
near to M/+ cells and activate transcription of Pvr, which acts through the ced-2,5,10,12 pathway to eliminate M/+ cells. Part of this pathway of M/+ cell
removal is common to the elimination of oncogenic scribbled mutant cells (Ohsawa et al 2011). In that context, JNK activity depends on eiger, the
Drosophila ortholog of TNF, rather than on Draper and Shark. Thus, two examples of cell competition converge on a common pathway of cell removal and
replacement that is also used in dorsal closure and wound healing. In addition, we have carried out a genetic screen to identify novel components of the
Draper pathway.
315C
Cell competition during adult gut homeostasis.
Golnar Kolahgar, Enzo Poirier, Sarah Mansour, Eugenia Piddini. The Gurdon Institute, University of
Cambridge, Cambridge, United Kingdom.
When a tissue is made of cells of different fitness levels, fitter cells induce death of less fit cells, in a sort of Darwinian selection process. This cellular
behavior, called cell competition, directly regulates tissue colonization during development and in some adult tissues both in the Drosophila and mouse
systems. We want to understand if cell competition regulates tissue homeostasis and cellular turnover in the adult fly intestine. In other words, are the cells
that begin to fail the ones that are replaced first to allow optimal gut function? By taking advantage of different mutations in the Minute genes, we
investigate how cell competition impacts on tissue homeostasis both in young and in ageing adult tissues. Specifically, we investigate how proliferation,
survival and cell fate decisions of stem and differentiated cells are affected when tissues are composed of cells of different fitness, and how that in turns
affects tissue homeostasis and organ physiology. We find that progenitor and stem cells renewal are locally affected but that the overall cell composition of
the tissue is not changed, suggesting that tissue turnover is locally responding to a phenomenon akin to cell competition.
316A
A model to study the influence of Hippo signaling on local cell-cell interactions.
Indrayani Waghmare
1
, Shilpi Verghese
1
, Katelin Hanes
1
, Alyssa Lesko
2
,
Amit Singh
1,3,4
, Madhuri Kango-Singh
1,3,4
. 1) Department of Biology, University of Dayton, Dayton, OH; 2) Department of Chemistry, University of Dayton,
Dayton OH; 3) Pre Medical Programs, University of Dayton, Dayton OH; 4) Center for Tissue Regeneration and Engineering at Dayton (TREND),
University of Dayton, Dayton OH.
The Hippo pathway regulates organ size from flies to mammals. Molecular genetic approaches in Drosophila established the crucial foundation of the
mechanisms of signal transduction and function of the Hippo pathway. Recent studies uncover a role for Hippo pathway in phenomena involving local cell-
cell interactions like cell competition or compensatory proliferation. Hyperactivation of Yorkie (Yki) is crucial for compensatory proliferation, cell
competition, and regenerative growth. We have studied the micro-environment of
scribble
(
scrib
) mutant cells to gain insights into the competitive ability of
scrib
mutant cells in the context of changes in Yki activity.
scrib
is a neoplastic tumor suppressor gene and loss of
scrib
in homozygous larvae causes
massive tumors to form. However, somatic clones comprising
scrib
mutant cells are slow growing and are competed out by the surrounding wild-type cells
by activation of JNK mediated apoptosis. We note that
scrib
mutant cells survive and proliferate when additional mutations in
scrib
mutant cells either
accelerate their proliferation or favor reduced cell competition (e.g., in
Minute
heterozygous background). We found that JNK and Hippo signaling both play
an important role in the growth and survival of scrib mutant cells. Furthermore, activation of JNK can suppress the over-growth of Yki over-expressing cells.
We decided to compare the clone size and Hippo pathway read-outs (
ex-lacZ, diap1-lacz or diap-GFP
) in five conditions viz.,
scrib
-/-
, scrib
-/-
M/+; scrib
-/-
+
P35, wts
-/-
scrib
-/-
and
RasV12 scrib
-/-
. Our preliminary data shows that the interaction of
scrib
mutant cells with the surrounding wild type cells differ for
each genotype. Here we present our analysis of Yki activity in
scrib
mutant cells challenged with different cell competitive environments.
317B
Regulation of Drosophila glial cell proliferation by Merlin-Hippo signaling.
venu bommireddy venkata, Ken Irvine. Waksman Institute, Piscataway, NJ.
Glia perform diverse and essential roles in the nervous system, but the mechanisms that regulate glial cell numbers are not well understood. Here, we
identify and characterize a requirement for the Hippo pathway and its transcriptional co-activator Yorkie in controlling Drosophila glial proliferation. We
find that Yorkie is both necessary for normal glial cell numbers, and, when activated, sufficient to drive glial over-proliferation. Yorkie activity in glial cells
is controlled by a Merlin-Hippo signaling pathway, whereas the upstream Hippo pathway regulators Fat, Expanded, Crumbs, and Lethal giant larvae have no
role. We extend functional characterization of Merlin-Hippo signaling by showing that Merlin and Hippo can be physically linked by the Salvador tumor
suppressor. Yorkie promotes expression of the microRNA gene bantam in glia, and bantam promotes expression of Myc, which is required for Yorkie and
bantam-induced glial proliferation. Our results provide new insights into the control of glial growth, and establish glia as a model for Merlin-specific Hippo
signaling. Moreover, as several of the genes we studied have been linked to human gliomas, our results suggest that this linkage could reflect their
organization into a conserved pathway for the control of glial cell proliferation.
318C
Hippo signaling controls Dronc activity to regulate organ size in Drosophila.
Shilpi Verghese
1
, Shimpi Bedi
1
, Madhuri Kango-Singh
1,2,3
. 1) Department
of Biology, University of Dayton, Dayton, OH; 2) Pre-Med Programs, University of Dayton, Dayton, OH, USA;; 3) Centre for Tissue Regeneration and
Engineering at Dayton (TREND), University of Dayton, 300 College Park Dayton, OH 45469 USA.
The Hippo signaling pathway regulates organ size by simultaneously inhibiting cell proliferation and promoting apoptosis. The Hippo pathway is
composed of a highly conserved core kinase cascade that is regulated by multiple upstream inputs and has multiple transcriptional outputs. Hippo signaling
is required for cells to stop proliferation when organs have reached their proper size and hippo mutant animals produce severely overgrown structures. In
contrast, over-expression of Hippo (or loss of yki) results in formation of smaller organs due to induction of apoptosis. Hippo pathway regulates apoptosis
through its apoptotic target genes e.g., Hid, DIAP1 and the microRNA bantam. We found that cell death induced by Hippo over-expression cannot be